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Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

ABSTRACT: (Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H?-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS). Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(P)RR levels in OSAS.

SUBMITTER: Takahashi K

PROVIDER: S-EPMC5486134 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

Takahashi Kazuhiro K Ohba Koji K Tajima Kazuki K Nishijima Tsuguo T Sakurai Shigeru S

International journal of molecular sciences 20170620 6

(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H⁺-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR ...[more]

PMID: 28632190

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Project description:BackgroundUnderstanding the causes and risk factors of metabolic syndrome is important for promoting population health. Oxidative stress has been associated with metabolic syndrome, and also obstructive sleep apnea. These are two diseases which have common prognostic characteristics for heart disease. The aim of this study was to examine the role of oxidative stress in the concurrent presence of metabolic syndrome and obstructive sleep apnea in a working population.MethodsParticipants were 163 artisan bakers in Shahroud, Iran, routinely exposed to significant heat stress and other oxidative stress indicators on a daily basis as part of their work. Using a cross-sectional design, data relevant to determining metabolic syndrome status according to International Diabetes Federation criteria, and the presence of obstructive sleep apnea according to the STOP-Bang score, was collected. Analyses included hierarchical binary logistic regression to yield predictors of the two diseases.ResultsHierarchical binary logistic regression showed that oxidative stress - alongside obesity, no regular exercise, and smoking - was an independent predictor of metabolic syndrome, but not obstructive sleep apnea. Participants who were obese were 28 times more likely to have metabolic syndrome (OR 28.59, 95% CI 4.91-63.02) and 44 times more likely to have obstructive sleep apnea (OR 44.48, 95% CI 4.91-403.28). Participants meeting metabolic syndrome criteria had significantly higher levels of malondialdehyde (p < 0.05) than those who did not. No difference in oxidative stress index levels were found according to obstructive sleep apnea status.ConclusionsOur findings suggest that oxidative stress contributes to the onset of metabolic syndrome, and that obstructive sleep apnea is involved in oxidative stress. Whilst obesity, exercise, and smoking remain important targets for reducing the incidence of metabolic syndrome and obstructive sleep apnea, policies to control risks of prolonged exposure to oxidative stress are also relevant in occupations where such environmental conditions exist.

Project description:BackgroundWe aimed to evaluate whether the severity of obstructive sleep apnea syndrome (OSAS) per se affects the prevalence of left ventricular (LV) diastolic dysfunction in patients without comorbidities.MethodsA total of 42 patients with first-diagnosed severe OSAS [apnea-hypopnea index (AHI) > 30] and 25 controls (AHI < 5), having been referred for snoring to the Sleep Laboratory Department of our tertiary Hospital, were enrolled in the study. Inclusion criteria were absence of any cardiovascular or oxidative stress-related comorbidities, and age between 20 and 70 years. Clinical, laboratory, echocardiographic, and polysomnographic data were recorded prospectively. Diastolic dysfunction diagnosis and grading was based on 2016 ASE/EACVI recommendations.ResultsSevere OSAS was associated with significantly increased prevalence and degree of diastolic dysfunction (26/42; 61.9%) compared with controls (7/25; 28%) (p = 0.007). AHI ⩾ 55 (dichotomous value of severe OSAS subset) was also characterized by greater prevalence and degree of diastolic dysfunction compared with 30 < AHI < 55 patients (p = 0.015). In the severe OSAS subset, age >45 years-old, height <1.745 m, body-mass index (BMI) >27.76 kg m-2, OSAS severity (AHI > 57.35), oxidative stress (overnight reduction of reduced to oxidized glutathione ratio < 18.44%), and BMI/height ratio > 16.155 kg m-3 (an index describing 'dense', short-heavy patients) presented significant diagnostic utility in identifying diastolic dysfunction in ROC-curve analysis (0.697 ⩾ AUC ⩾ 0.855, 0.001 ⩽ p ⩽ 0.018). In binary logistic regression model, advanced age (OR 1.23, 95% CI 1.025-1.477; p = 0.026) and AHI (OR 1.123, 95% CI 1.007-1.253; p = 0.036) showed independent association with diastolic dysfunction in severe OSAS.ConclusionsThe present prospective study may suggest that severe OSAS is significantly associated with LV diastolic dysfunction; OSAS clinical severity exerts a positive influence on (and possibly constitutes an independent risk factor of) LV diastolic dysfunction. The reviews of this paper are available via the supplementary material section.

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Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

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Soluble (Pro)renin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

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